Link to Pubmed [PMID] – 27016457
Fertil. Steril. 2016 07;106(1):225-229.e11
OBJECTIVE: To determine the genetic cause of 46,XY primary amenorrhea in three 46,XY girls.
DESIGN: Whole exome sequencing.
SETTING: University cytogenetics center.
PATIENT(S): Three patients with unexplained 46,XY primary amenorrhea were included in the study.
INTERVENTION(S): Potentially pathogenic variants were confirmed by Sanger sequencing, and familial segregation was determined where parents’ DNA was available.
MAIN OUTCOME MEASURE(S): Exome sequencing was performed in the three patients, and the data were analyzed for potentially pathogenic mutations. The functional consequences of mutations were predicted.
RESULT(S): Three novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene were identified:c.1573 C→T, p.Gln525Ter, c.1435 C→T p.Arg479Ter, and c.508 C→T, p.Gln170Ter.
CONCLUSION(S): Inactivating mutations of the LHCGR gene may be a more common cause of 46,XY primary amenorrhea than previously considered.